We propose to develop a new transvaginal imaging device using co-registered photoacoustic and ultrasound technique for dual-modality non-invasive detection and characterization of ovarian cancer and abnormality in situ. The photoacoustic technique provides optical contrast of tumor angiogenesis and tumor hypoxia with ultrasound (US) resolution for deeply seated lesions of up to 3-4 cm. The ability to image early angiogenesis changes as well as tumor hypoxia in the ovary with this non-invasive imaging modality would greatly enhance the care for women at risk for ovarian cancer. Data obtained from our ex vivo imaging of normal, abnormal and malignant ovarian tissue have demonstrated that there is a significantly different angiogenic formation when malignant cancers and abnormal ovarian tissues are compared to normal ovarian tissues. We have developed a prototype co- registered photoacoustic and US system, which allows us to validate the hypothesis that this new imaging device will improve the current clinical practice for non-invasive diagnosis of early stage ovarian cancers and ovarian abnormality and will guide surgical intervention of high-risk ovarian cancer patients. In this proposal, we will 1) develop a transvaginal photoacoustic/US probe and system suitable for in vivo dual-modality non-invasive detection and characterization of the ovary;2) characterize normal, abnormal and cancerous ovarian tissue ex vivo by comparing imaging results with histopathology and microvessel density counts and distributions as well as average optical absorption;3) evaluate the prototype probe for in vivo imaging of patients who are scheduled for prophylactic oophorectomy;4) monitor a group of high-risk premenopausal women during their menstrual cycles to determine the cyclic changes in functional and morphological parameters that may differ from angiogenesis changes associated with the malignant process. Approximately 60 patients will be recruited for the ex vivo study in Aim 2, which will allow us to validate the initial sensitivity and specificity of the proposed technique. Approximately 40 patients will be recruited for the in vivo study in Aim 3, which will allow us to evaluate the technique and validate the ex vivo results. Approximately 20 to 25 premenopausal high- risk patients will be recruited for the in vivo study in Aim 4, which will allow us to assess the efficacy of this new technique within a premenopausal population. The successful completion of the project will provide a means to improve the current clinical practice: it will provide necessary technology to improve the ability to determine if a cancer is present and to avoid surgery in a substantial number of women. PUBLIC HEALTH RELEVANCE: In this project, a new transvaginal imaging device optimized for ovarian cancer detection and diagnosis will be developed and validated from ex vivo and in vivo clinical studies. We will study ovaries from both premenopausal and postmenopausal women with normal, abnormal and malignant ovarian tissue in an attempt to provide a more cost effective and accurate diagnostic technique to aid doctors and patients in determining the need for surgery. Current technologies (ultrasound, CT, MRI, PET, CA125 and physical exam) provide insufficient data to determine whether an ovary must be removed or is likely cancerous;therefore, a better method is needed to determine if ovarian tissue is malignant or benign. The successful completion of the project will provide a means to improve the current clinical practice;it will provide necessary technology to improve early ovarian cancer detection;and it will be an effective means to avoid surgery in most patients with a normal ovary. It is also a relatively inexpensive technology and, if accurate, would substantially reduce medical costs and provide women with a better determination of their risk of cancer and thus improve their quality of life.